Phospholipase C isozymes (PLCs) catalyze the conversion of the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Scheme 1).1 IP3 mobilizes intracellular stores of Ca2+ while DAG activates protein kinase C.2 Furthermore, depletion of PIP2 alters the membrane association and/or activity of many proteins that harbor phosphoinositide binding domains.3 Consequently, PLC isozymes are key signaling proteins that regulate the physiological responses of many extracellular stimuli such as hormones, neurotransmitters, and growth factors. Aberrant regulation of PLCs has been implicated in various diseases including cancer, Alzheimer's disease, and others.4 Although extensive studies have been carried out to understand PLC regulation, two limitations remain: 1) it is difficult to monitor PLC activity in living cells; and 2) selective small molecule PLC inhibitors are lacking.5

The present invention overcomes previous shortcomings in the art by providing compounds and methods for detecting phospholipase C (PLC) activity.